Action Points

Hospitalization for certain types of infection during childhood (respiratory tract infection for example) influenced the likelihood of an individual's later development of ankylosing spondylitis (AS).

Note that although causality could not be determined for the associations that were identified, it is possible that the different infections during childhood could induce long-lasting immunological effects that may affect the disease onset in genetically predisposed individuals.

Hospitalization for certain types of infection during childhood influenced the likelihood of an individual's later development of ankylosing spondylitis (AS), Swedish researchers found.

For instance, children who were admitted for a respiratory tract infection had increased odds for being diagnosed with AS in adulthood of (OR 1.24, 95% CI 1.07-1.44), and the risk was even higher when tonsillectomy was performed (OR 1.38, 95% CI 1.06-1.77), relative to children not hospitalized with infections, according to Ulf Lindstrom, MD, of the University of Gothenburg, and colleagues.

But this was not true for all infections: hospitalization for appendicitis, for example, was associated with decreased risk (OR 0.59, 95% CI 0.41-0.83), as was appendectomy (OR 0.73, 95% CI 0.55-0.97), the researchers reported online in Arthritis Research & Therapy.

It's well recognized that genetic factors play a strong role in the etiology of AS, and in particular the HLA-B27 gene. And although few studies in AS have examined the potential for environmental factors that might also contribute, in other rheumatic/inflammatory diseases such as rheumatoid arthritis, environmental factors such as smoking have been clearly linked.

In addition, a related spondyloarthritic condition, reactive arthritis, typically is triggered by urogenital or enteric infections, while psoriasis -- another member of the spondyloarthritis group of diseases -- can be triggered by streptococcal tonsillitis.

For AS, "the two most prevailing theories suggest that onset of AS in genetically susceptible individuals may be triggered by either infections or by mechanical stress, and sparse data also suggest an association with smoking," Lindstrom and colleagues wrote.

To explore the possible link between infection and later AS, the researchers conducted a case-control study of data from four Swedish national registers. Cases of AS were identified from the specialized care outpatient register from 2001 to 2010, and up to five controls for each case were matched from the general population register.

The analysis included 2,453 cases and 10,257 controls. Almost two-thirds were men, and the age at AS diagnosis was 30.6 years.

Among cases, 17.4% had been hospitalized for any infection before age 17, as were 16.3% of controls, which did not differ significantly (OR 1.08, 95% CI 0.96-1.22). Unlike for respiratory infections and appendicitis, no associations were found for enteric or urogenital infections.

The researchers also considered the risk among patients with both tonsillitis and tonsillectomy, and found an odds ratio of 1.38 (95% CI 1.04-1.78). For those with both appendicitis and appendectomy, the odds ratio was 0.60 (95% CI 0.42-0.85).

They further conducted several sensitivity analyses, which showed similar results as the primary analysis. In one analysis that stratified patients according to median age at the time of AS diagnosis (under or over 30), "all point estimates were in the same direction and of similar magnitude as in the primary analysis, apart from tonsillitis and tonsillectomy, which were stronger in the younger age groups," the researchers noted.

For those who were younger than 30 at the time of AS diagnosis, the odds ratios were 1.15 (95% CI 1.13-2.94) for tonsillitis and 1.65 (95% CI 1.21-2.26) for tonsillectomy. For those who were older than 30, the odds ratios were 0.97 (95% CI 0.62-1.51) and 0.94 (95% CI 0.59-1.51), respectively.

The median ages for tonsillectomy and appendectomy were 9 and 12 years, respectively. In an analysis stratified according to age at appendectomy, the decreased risk was more pronounced in those younger than 12 at the time of the procedure (OR 0.61, 95% CI 0.42-0.89) than for those older than 12 (OR 0.95, 95% CI 0.63-1.43). For tonsillectomy, the increased risk was similar regardless of whether the procedure took place before or after age 9.

The authors cautioned that causality could not be determined for the associations they identified. "Still, it cannot be ruled out that the different infections during childhood could induce long-lasting immunological effects that may affect the disease onset in genetically predisposed individuals," they stated.

They specifically emphasized a connection to the HLA-B27 gene, noting that variants in this gene have been associated with alterations in host response to different pathogens. "It is possible that the immune phenotype of AS, including HLA-B27, leading up to the development of AS also conveys a hitherto unknown increase in risk for respiratory tract infections and a decrease in risk for appendicitis," they suggested.

Further studies will be needed clarify whether the associations seen in this study reflect the influence of the immune phenotype or the infections themselves, they concluded.

The study was funded by the Swedish Research Council, the Region Vastra Gotaland, the Stockholm County Council, the Swedish National Rheumatism Association, and the Swedish Foundation for Strategic Research.

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